SLC36A1

Chr 5

solute carrier family 36 member 1

Also known as: Dct1, LYAAT1, PAT1, TRAMD3

The protein functions as an electrogenic proton/amino acid symporter with selectivity for small neutral amino acids and GABA, and may be involved in lysosomal amino acid efflux and neuronal exocytosis. Mutations cause autosomal recessive iminoglycinuria with hyperglycinuria, a benign renal transport disorder typically presenting in childhood with elevated glycine and imino acids in urine. The gene shows low constraint to loss-of-function variation, consistent with the mild clinical phenotype.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.90
Clinical SummarySLC36A1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.90LOEUF
pLI 0.000
Z-score 1.92
OE 0.57 (0.370.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.38Z-score
OE missense 0.77 (0.690.86)
220 obs / 285.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.370.90)
00.351.4
Missense OE0.77 (0.690.86)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 13 / 22.9Missense obs/exp: 220 / 285.6Syn Z: 0.03
DN
0.77top 25%
GOF
0.82top 10%
LOF
0.1796th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC36A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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